Lactoferrin (LF) is an iron binding protein synthesized by neutrophils and glandular epithelial cells. LF has been detected in most of the major secretions that bathe human mucosal surfaces; including saliva. Previous studies have indicated that LF, can reversibly inhibit the growth of a variety of microorganisms by binding available iron making it inaccessible to the bacteria. This inhibition is readily reversed by the addition of exogenous iron. Recent studies in our laboratory have indicated that LF is capable of a direct irreversible inhibition of certain bacteria. This bactericidal effect is dependent on the chelating properties of LF. A survey of microorganisms indicated that a number of oral microorganisms were susceptible to the bactericidal activity of LF, suggesting a potential potent mechanism for the regulation of the oral flora by salivary LF. Current studies are being directed at a survey of a variety of LF susceptible and resistant microorganisms. Through such studies it may be possible to determine the mechanism of bacterial resistance and indirectly the mode of LF action. Possible interactions between LF and other salivary components such as antibody, lysozyme and lactoperoxidase are also being investigated with either purified components or in saliva from various immune deficient and control subjects. The in situ effects of LF will be investigated by analyses of localization and quantitation of LF in dental plaque and plaque free-fluid. The effects of LF on colonization of various oral microorganisms are being evaluated in an in vitro system.